The normal metabolism of the branched-chain amino acids , leucine, isoleucine, and valine, involves loss of the α-amino group, followed by oxidative decarboxylation of the resulting α-keto acid. This decarboxylation step is catalyzed by branched-chain keto acid decarboxylase, a multienzyme complex, associated with the inner membrane of the mitochondrion. In approximately 1 in 300 000 live births, a defect in this enzyme leads to accumulation of the keto acids corresponding to these branched-chain amino acids in the blood, and then to branched-chain ketoaciduria. When untreated or unmanaged, this condition may lead to both physical and mental retardation of the newborn and a distinct maple syrup odor of the urine. This defect can be partially managed with a low-protein or modified diet, but not in all cases. In some instances, supplementation with high doses of thiamine pyrophosphate, a cofactor for this enzyme complex, has been helpful.
|
